Exercise capacity is extremely low in patients with end stage renal disease (ESRD) treated with conventional hemodialysis, and improves significantly shortly after successful transplantation. It is suspected that factors associated with uremia impair the normal integration of physiological systems required for increased oxygen transport and utilization during exercise. There is growing interest in slow daily hemodialysis(both short daily hemodialysis and slow nocturnal hemodialysis), which increases the dialysis provided and reduces uremic signs and symptoms. We propose to study patients with ESRD treated with 4 different modalities: conventional hemodialysis (CHD) (3days/week, 3 hours/treatment), low nocturnal hemodialysis (SND), short daily hemodialysis (SDD) and living donor transplantation (RTX) to assess differences in physiological responses to and determinants of exercise. The hypothesis is that physiological responses to exercise and the determinants of exercise in patients treated with daily hemodialysis are more normal compared to conventional hemodialysis and similar to those of transplant recipients. Testing will be performed to measure the following: exercise capacity (VO2max), cardiac output, a-vO2difference, endothelial function (brachial artery reactivity), autonomic function (24 hour heart rate variability), muscle blood flow (calf plethysmography with doppler), leg muscle mass (magnetic resonance imaging), muscle ultrastructure (muscle biopsy analysis), muscle function (isokinetic muscle testing), and oxidative capacity (magnetic resonance spectroscopy), total body composition (dual energy x-ray absorptiomtetry), and quality of life (KDQOL). This study will provide new information on the limitations to functioning in uremic patients and provide physiological comparisons of the various ESRD treatment modes. The relationship between and contributions of the various physiological measures to exercise capacity will also be revealed. The results of this study will be important in guiding the nephrology community in improving dialysis treatments so patients can be directed into therapies that are found to achieve higher levels of functioning and thus possibly improve rehabilitation and quality of life.